With over 100 apparently unique metabolites in the Cannabis plant, there are a plethora of potential molecular targets. The molecular actions of Δ9-tetrahydrocannabinol are the best-investigated, which have centred mostly on a relatively high-potency, low-efficacy action at the CB1 cannabinoid receptor. By contrast, cannabidiol has a multitude of lower potency molecular targets identified in vitro, but with limited clarity about their relevance for the effects of cannabidiol in humans. This review highlights the incomplete nature of studies of the major phytocannabinoids, particularly the acid phytocannabinoids.

Among the complications associated with the use of classic psychedelics, flashbacks, hallucinogen persisting perception disorder (HPPD) and reactivations are most specifically linked to their use. These three phenomena share the occurrence of perceptual disturbances resembling those experienced under the acute effects of psychedelics, but HPPD differs from flashbacks and reactivations due to its persistent nature.Existing evidence suggests that HPPD has a generally low relative prevalence, though in some cases, it may reach considerable clinical relevance. In contrast, flashbacks and reactivations may be more common but are less frequently documented, as they typically do not result in significant distress or treatment-seeking behavior.Many patients presenting with post-psychedelic complications assume they have HPPD; however, only a minority actually meet diagnostic criteria, with others suffering from different psychedelic-related complications. This complicates epidemiological estimates of HPPD and underscores the importance of comprehensive differential diagnostic assessment. Subsuming non-pathological phenomena like flashbacks to HPPD inappropriately inflates prevalence estimates.In very rare cases, HPPD may develop into a chronic condition requiring long-term pharmacological treatment, while in most cases, HPPD spontaneously subsides within one year or diminishes to a tolerable level. It is therefore essential to avoid emphasizing negative prognoses, as they may influence treatment outcomes.This chapter provides an overview of the phenomenology, epidemiology, diagnostic classification, and differential diagnoses of flashbacks, HPPD, and reactivations. As evidence-based treatment options are not yet available, current knowledge is derived from case reports and clinical experience.

Alongside the important contributions of the harm reduction movement to improving public health in secular settings, communities that use psychedelics as religious sacraments (i.e., entheogens) have developed their own frameworks for supporting safety within their spiritual practices and hold their own conceptualizations of risk and harm. In order to understand better the lived realities of substance use, safety practices, and potential harms among entheogenic communities, researchers can collaborate closely with these communities in the formulation and conduct of their studies in this shared pursuit. The integration of community-based participatory research (CBPR) practices can not only help center these communities in the co-creation of research but also improve engagement, generate trust, and illuminate local priorities for knowledge production. The current work presents preliminary findings from a CBPR study with entheogenic communities. We share "lessons learned" from forming the study's community advisory board (CAB) and initial pilot data gathering in order to encourage biomedical investigators to consider CBPR approaches for their own research with psychedelic communities. Lessons include consultation with community engagement experts; considerations for compensation and confidentiality; utilizing multimodal strategies for recruiting study participants and CAB members; and the importance of considering the unique historical context of these communities. These lessons support the development of best practices for current and future psychedelic research as well as subsequent policies and public education efforts focused on psychedelic harm reduction and the community-based uses of psychedelics more broadly.

Touch has long been an essential element in human communication and healing. In the field of psychedelic-assisted therapy (PAT), the role of touch (and by extension, non-touch) presents complex ethical and practical challenges, particularly due to the heightened vulnerability of individuals in altered states of consciousness. Recent public discourse, including reports of boundary violations and abuse, has sharpened the political and ethical discussion around physical contact in PAT settings.This chapter approaches the topic from a harm reduction perspective, acknowledging the risks of misuse and the need for clear boundaries, transparency, informed consent, and cultural sensitivity. At the same time, we argue that touch can offer grounding, emotional support, and therapeutic value when used with care and responsibly. We explore both touch and non-touch interventions in PAT, examining their historical roots, therapeutic potentials, and outlining the ethical frameworks necessary to navigate this complex and sensitive terrain. Our aim is to contribute to an informed and nuanced dialogue on the topic, which supports safe, ethical, and effective therapeutic practices.

Classic psychedelics such as LSD, psilocybin, and DMT from unregulated markets pose considerable risks through unknown adulterants and potencies. In this chapter, we explore the importance of drug checking in minimizing harm among users of classic psychedelics and examine the opportunities and challenges associated with intervention settings, analytical techniques, and risk communication strategies. Gas chromatography (GC) and liquid chromatography (LC) coupled with mass spectrometry (MS) provide the most reliable and comprehensive analysis results for classic psychedelics. However, they are relatively costly, stationary, and require legal permission to obtain reference standards. Combined presumptive tests, such as thin-layer chromatography (TLC) and reagent testing, offer a time-efficient and cost-effective approach to initial substance screening. For certain compounds, Fourier-transform infrared spectroscopy (FTIR) serves as a valuable complementary technique, although potent psychedelics, such as LSD and NBOMe on blotter paper or in diluted solution, and complex botanical matrices challenge its detection limit, requiring the use of multiple analytical methods to confirm results. Such combination can effectively prevent acute risks, while confirmatory instrumental analysis remains essential for ongoing monitoring and public health efforts. Alongside robust testing procedures, drug checking's consultative component is crucial for clarifying analytical constraints, promoting safer use practices, and offering referrals to health services. By identifying mislabeled samples and ensuring tailored risk communication, drug checking not only protects individual users but also informs the public and health professionals regarding dangerous or novel substances. This chapter situates drug checking as a key public health measure that reduces acute harm from misrepresented psychedelic substances while supporting monitoring efforts.

Depersonalization (DP) and Derealization (DR) refer to perceptual changes of "as-if-character" where the self (→DP) or the surroundings (→DR) are experienced as unreal. These symptoms are highly prevalent in individuals with mental disorders. If these symptoms persist most of the day for months, the diagnosis of depersonalization-derealization-disorder (DDD) is likely. DDD is a common disorder with a high comorbidity with depression, anxiety disorders, and personality disorders.The intake of classic psychedelic drugs often elicits DP/DR symptoms, which cease in most cases when the drug is eliminated. DDD is frequently precipitated by drug intoxication (cannabis and classic psychedelics). Patients and some researchers assume, therefore, that drug intoxication is the cause of DDD and frame it as a "never-ending trip." Researchers base their assumption on the potential of psychedelics to elicit DP/DR symptoms and on case series of individuals reporting long-lasting uncomfortable symptoms after drug intake. Arguments are presented that demonstrate this is a reductionist conclusion and that this assertion may lead to false illness perceptions, hinder awareness of emotional conflicts, and erode patients' self-efficacy. The main arguments are that, first, DDD is a mental disorder resulting from the avoidance of aversive emotional states. DDD is related to functional alterations of brain networks rather than organic brain damage. Second, psychedelics act as a catalyst that accelerates the onset of DDD in vulnerable individuals by mobilizing complex anxiety-laden unconscious emotions from early attachment traumas.The treatment of DDD encompasses psychoeducation about the nature of the disorder, challenging false causal attributions to external causes (such as drug intake) and helping the patient experience and process their emotions adaptively. To achieve remission, patients usually need long-term psychotherapy of 50-100 sessions.

Psychedelic substances have been increasingly recognised for their potential in treating various mental health conditions, yet they can also induce what we call ontologically challenging psychedelic experiences (OCPEs), a concept developed in our research to describe experiences that profoundly disrupt an individual's sense of self, reality, and existence. We present OCPEs not as a diagnostic category but as a phenomenological and harm reduction perspective on certain destabilising psychedelic experiences.While some individuals integrate OCPEs with ease, others struggle with ontological instability, existential distress, and impairments that persist long after acute effects. Importantly, ontological challenges are not always negative: for many, when they feel adequately resourced, they form part of the therapeutic mechanism and are a valued opportunity for personal development and growth. Drawing on our qualitative studies alongside other psychological research, we examine the phenomenology of OCPEs and their challenging aftermath, as well as strategies that may help facilitate recovery and integration. Grounding techniques, cognitive (re)framing, and supportive structures are discussed as potentially beneficial approaches and resources.Finally, we outline ethical and practical implications for clinical and harm reduction practice. We highlight the limits of informed consent in psychedelic therapy and argue for the value of preparation and post-experience support that is attuned to ontological disruptions. As empirical evidence remains limited, further research is needed to refine best practices. The development of an ethically responsible approach, informed by the phenomenology of OCPEs, can help maximise benefits of psychedelic substances while minimising long-term harm.

Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to treat maternal depression during pregnancy, yet their potential impact on foetal brain development remains a concern. Although maternal illness is a known confounder, growing evidence from both clinical and preclinical studies suggests that perinatal SSRI exposure may independently influence neurodevelopmental outcomes. This review draws on rodent studies to explore how developmental SSRI exposure affects the gut microbiome, maternal behaviour, myelination, and offspring social behaviour. Elevated serotonin levels caused by SSRIs can alter both brain development and the maternal gut microbiota, with possible long-term effects on offspring. Behaviourally, SSRI-exposed offspring often show reduced social play, altered social interactions, and sex-specific effects on aggression and sexual behaviour, in which males appear more sensitive to these effects than females. Maternal care is only modestly affected. Overall, developmental SSRI exposure in the absence of maternal illness can disrupt brain development and social behaviour in offspring, potentially through gut-brain axis mechanisms and altered myelination.

Alcohol use disorder (AUD) is a debilitating condition affecting over 30 million Americans. AUD commonly co-occurs with other disorders, like other substance use disorders, trauma-related disorders, and anxiety disorders. Of the numerous co-occurring disorders, anxiety disorders are the most pervasive: anxiety disorders serve as a risk factor for developing AUD, emerge as co-occurring disorders that maintain alcohol drinking, and impede the effectiveness of treatments for AUD. Anxiety, therefore, shapes the development, course, and treatment of AUDs. AUDs can also increase anxiety, suggesting a complex, bidirectional relation between alcohol use and anxiety. The intersection of AUDs and anxiety is also supported by their overlapping neural circuits, specifically neural circuits involved in stress responding, reward processing, and cognitive control. The current review highlights findings from several decades of research on how anxiety impacts the brain and treatment outcomes in AUDs. We also provide important considerations for future research, with the goal of reducing the shame and burden of alcohol use for individuals with AUD and their families.